69: Prionlike Proteins Help Form Memories

Prions, the rogue proteins that cause mad cow disease, may turn out to be more than just relentless killers. Nobel laureate Eric Kandel, a neuroscientist at Columbia University in New York City, and his postdoctoral student Kausik Si reported last winter that a protein bearing a close resemblance to a prion plays a key role in the formation of long-term memories. Their study also suggests that prionlike proteins—which can change shape and, unlike other proteins, also induce neighboring proteins to change shape—are not as anomalous as they once seemed. “This is unlikely to be an isolated case in all of biology,” Kandel says. “And I don’t think this need be uniquely a brain function.”

For years Kandel has probed the mysteries of memory by studying the nervous system of the simple sea slug. He knew that a protein called CPEB was involved in strengthening connections between neurons, an essential part of the process of memory formation. What he did not understand was how these connections could remain stable enough to last for days, months, or years, as memories do. Then Si noticed a molecular similarity in CPEB to a harmless prion protein found in yeast. After consulting with Susan Lindquist, a yeast-prion expert at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, Kandel and Si fused the slug protein with the yeast-prion protein and found that the yeast-friendly CPEB acted like a prion, shifting shape and causing the proteins all around it to act identically in a very durable way. If such a prion-induced chain reaction also occurs with the CPEB in the human brain, the scientists speculate, it could provide an unusually durable foundation for storing memories. This process is so efficient, Lindquist says, “we think it’s actually a very ancient, very old mechanism.”